The present invention relates to methods and apparatus for pumping small volumes of fluid, particularly where small volumes of fluid are to be transferred from one container to the other.
Automated liquid handling systems have become a standard part of many biological laboratories. In a typical configuration a robot or motion system is coupled with a syringe or peristaltic pump (such as the Biomek configuration by Beckman Coulter, Inc.). Such systems are fairly effective in transferring liquid samples in the 1 xcexcl or larger range from one container to the other. However, they do not generally provide reliable transfer of sample volumes smaller than 1 xcexcl.
Devices are known for through pumping of small fluid quantities. For example, U.S. Pat. Nos. 5,094,594, 5,730,187 and 6,033,628 disclose devices which can pump fluid volumes in the nanoliter or picoliter range. However, these devices are arranged so that the fluid sample is pumped through them. Such devices are not convenient for simply transferring fluid from one container to another where it is desired to aspirate and expel the fluid from the same opening in the manner of a pipette. This is so since with very small fluid samples some of the fluid will wet and remain in the pumping mechanism itself. The pumping mechanism then, becomes a source of sample cross-contamination unless cleaned.
It would be desirable then if a means could be provided which allowed for transfer of very small samples of relatively precisely controlled volume. It would further be desirable if such means allowed the surfaces contacted by the fluid to be separable and replaceable from the remainder of the device.
The present invention then, provides in one aspect a microfluidic pumping method. This method uses an apparatus with a pulse jet and a working fluid in the pulse jet. The pulse jet, in response to activation by a set of electrical pulses, moves corresponding pulses of fluid from a first to a second side of the pulse jet. A chamber with an opening, is in pressure communication with the first side of the pulse jet such that activation of the pulse jet causes a reduced pressure at the opening. The method includes contacting the opening (which in one particular aspect, may initially be open to ambient atmosphere but need not be in all aspects of the invention) with a sample fluid and activating the pulse jet so as to draw the sample fluid into the chamber (sometimes referenced as xe2x80x9cloadingxe2x80x9d the sample). The chamber may or may not be partly empty of sample or any fluid before contacting the opening with the sample fluid. Optionally the opening and first side of the pulse jet may be in fluid isolation from one another, and the sample and working fluids may be maintained in isolation (that is, from one another), such as by an intervening gas (such as air) or liquid immiscible with the working and sample fluids, or by the sample and working fluids being different and immiscible with one another. Optionally, the method may include any suitable arrangement for discharging the loaded sample through the opening (for example, a second pulse jet as described further below). However, such arrangement need not allow for precise volume control of ejected sample since, with the sample and working fluids in isolation and when all the sample in the chamber is to be discharged, a precise volume was already determined by the pulse jet during sample loading into the chamber. Thus, the suitable arrangement mentioned could be a valve and pressure source for applying a pressure differential to the loaded sample.
Another aspect of the method uses an apparatus with a pulse jet head having first and second pulse jets and a working fluid in the head. The first pulse jet, in response to activation by a set of electrical pulses, moves corresponding pulses of fluid from a first side of the head to a second side. The second pulse jet, in response to activation by a set of electrical pulses, moves corresponding pulses of fluid from the second side of the head to the first side. A chamber with an opening is in pressure communication with the first side of the head, such that activation of the first pulse jet causes a reduced pressure at the opening and activation of the second pulse jet causes an increased pressure at the opening. In the aspect of the method, the opening is contacted with a sample fluid and the first pulse jet is activated so as to draw a sample fluid through the opening and into the chamber (that is, the sample is loaded). The second pulse jet may be activated so as to discharge loaded sample fluid through the opening.
Optionally, the opening may be a capillary opening, or the chamber may even comprise a capillary conduit which extends to the first pulse jet first side. Either configuration can assist in retaining sample fluid in the chamber prior to discharging it.
The present invention also provides a microfluidic pump of any of the configurations described above. The opening may be in pressure communication with the first side of the first pulse jet through, for example, a conduit shaped to maintain sample and working fluids in isolation. Such a configuration allows pressure communication but can maintain sample and working fluids in isolation from one another. Alternatively, a flexible diaphragm between the opening and the first side of the pulse jet head could be used for this purpose. Optionally, each pulse jet may have one or two check valves each on an inlet or outlet side of the pulse jet, to inhibit a backward flow through the pulse jets.
The various aspects of the present invention can provide any one or more of the following and/or other useful benefits. For example, very small volumes of samples can be transferred with relatively precisely control. It is not necessary that sample fluid contact internal pumping parts. The construction allows for surfaces contacted by the sample fluid to be separable and replaceable from the remainder of the device.